Comprehensive genomic profiling (CGP) of esophageal and tubular GI tumors to identify frequencies of ErbB family member amplification with therapeutic implications.

Abstract

8 Background: As described in the MyPathway study, amplification and other mutations in ErbB-family proteins are actionable events across solid tumors. Targeting ERBB2 amplifications (amp) in tubular GI cancers (TGC) improves patient outcomes. ErbB family comparisons across anatomic sites is lacking and here we describe the largest known series in TGC. Methods: DNA was extracted from 12,685 FFPE clinical TGC specimens, including 1,720 esophageal CA*. CGP was performed on hybrid-capture, adaptor ligation based libraries to a mean coverage depth of 720X for up to 315 genes plus 47 introns from 19 genes frequently rearranged in cancer. Results: Across all TGC cases, amp was the most frequent genomic alteration among ErbB members at 8.7%. ERBB2 amp was 2.3x as common as EGFR amp across TGC. Across TGC sites, EGFR amp was most frequent in esophageal SCC (13.7%) and ERBB2 amp was most common in gastroesophageal junction adenoCA (21%) compared with overall frequencies of 2.7% and 5.5% respectively. ERBB3 and ERBB4 amp were rare, and most common in gastroesophageal adenoCA relative to other TGC. Clinical support with outcomes for patients treated with anti-ErbB targeted therapy across TGC will be presented, including profiling from cases of acquired resistance to anti-ErbB targeted therapy. Conclusions: Among TGC, esophageal CA harbored the most ErbB family member amp with variation by histology. Profiling across ErbB proteins in TGC suggests biologic differences and may affect response to treatment. CGP can expand the population who may benefit from anti-ErbB directed therapies and refine treatment choices. Further research is warranted. [Table: see text]